This invention relates to the field of hemodialysis.
The life expectancy of patients with irreversible renal failure can be prolonged by hemodialysis using an extracorporeal circuit including a dialyzer (or artificial kidney). As there is no specific measurable toxin in the blood of such patients, the provision of a "dose" of treatment has been, for the most part, trial and error. A physician bases the dialysis prescription often empirically, or if on some concept, on for instance, the effect on patient well-being or on blood levels of waste such as creatinine or urea. Currently, the hemodialysis procedure for patients with end stage renal failure involves treatment three times per week for three to six hours, with the majority of patients in North America being dialyzed for four hours or less.
The lack of understanding of the pathogenesis of uremia has made it difficult, and continues to make it difficult, to clearly define an adequate dialysis prescription. Because of a dispute over which uremic toxins were important and because of the clear need for a quantifiable approach for the dialysis prescription, the National Cooperative Dialysis Study (NCDS) was undertaken in the 1970's and has been a source of continual review since its publication in the 1980's.
At any point in time during dialysis, the blood concentration of urea depends on its rate of generation, its volume of distribution, the residual renal function, the clearance of the dialyzer, and the elapsed dialysis time. The clearance of the dialyzer will depend upon the nature of the membrane, the effective membrane surface area, the blood flow rate, and the dialysate flow rate.
The normalized dose of dialysis can be defined for urea by the dimensionless parameter Kt/V, where K is the clearance of urea by the dialyzer (ml/min), where t is time (min.), and where V is the volume of distribution of urea (ml). Current methods of calculating Kt/V (urea) are complex and require accurate measurement of the dialyzer urea clearance and subsequent calculation of the volume of distribution of urea. The only accurate way of determining the dialyzer urea clearance and volume of urea distribution is to collect the total dialysate and assay the urea content, and the logistic problems of this approach prevent its general use.
One study involving a mechanistic analysis of the NCDS data has indicated that the probability of uremic manifestations is high (57%) and constant over the treatment range 0.4.ltoreq.Kt/V (urea).ltoreq.0.8, and that over the treatment range 0.9&lt;Kt/V (urea)&lt;1.5, there is a sharp decrease in morbidity to a constant 13%. Other studies have confirmed that a Kt/V (urea) of 1 or more should be targeted.
However, each dialysis is not equal. Patients may not receive the prescribed Kt/V (urea) for various reasons including decrease in blood pressure and decreased blood flow rates.
Work by Jindal and co-workers utilizes the equation Kt/V=0.04 PRU-1.2, and has indicated that a percent reduction in blood urea concentration (PRU) of approximately 55 during hemodialysis is necessary to obtain a Kt/V (urea) of 1. More recently, Daugirdas has argued that the PRU may result in Kt/V (urea) values substantially above or below the target Kt/V, and suggested the formula Kt/V=-ln (R-0.03-UF/W), where R is the post/predialysis plasma urea ratio, where 0.03 is a constant that allows for urea generation during dialysis, where UF is the prescribed ultrafiltration volume (1) over dialysis, and where W is the prescribed post-dialysis weight (kg).
Increasing numbers of nephrologists are using various methodologies for calculating Kt/V (urea) as a basis for the dialysis prescription. However, at present, few renal units are using any form of urea kinetics to aid in the dialysis prescription, and a recent study shows that even in a dialysis unit using urea kinetic modelling on a regular basis, the prescribed dose of dialysis Kt/V is frequently not achieved.
Furthermore, in this current time of economic restraint, there is pressure upon health care teams to consider cost efficiency in therapeutic strategies. To the nephrologist, this may mean shortening dialysis time by using a device "more efficient" in removing uremic toxins.
As illustrated by U.S. Pat. Nos. 4,231,366 to Schael and 4,897,184 to Shouldice et al, computer automation of hemodialysis has been considered in which sensor signals are inputted to a control circuit, condition control is effected, conditions are monitored to be within a predetermined limit, and a failure to be within the limit is signalled. Schael uses this automated approach to maintain patient blood flow within predetermined limits, due to the effect of blood flow on time for dialysis. However, computer automation has not been employed to predict a time endpoint for dialysis.
Accordingly, there is a need for an improved hemodialysis method based upon urea kinetics. Advantageously, the method would provide guaranteed dose hemodialysis, that is, would target the optimization of each dialysis treatment and no longer rely upon dialysis treatments equal in time as in the Schael approach. Beneficially, the improved hemodialysis method would provide cost savings. Preferably, the method would be automated and could predict a time endpoint for dialysis. If so, better scheduling of patients would result.